THE MOLECULAR-BASIS OF GROWTH-HORMONE ACTION

Recent studies have begun to elucidate the molecular actions of growth hormone, a major regulator of somatic growth and metabolic functions. The cell surface growth hormone receptor, a member of the cytokine re ceptor superfamily, binds as a dimer to a single growth hormone molecu le. Receptor dimerization precedes signal transduction, which is predo minantly mediated by the non-receptor tyrosine kinase, Jak2. Activatio n of Jak2 leads to mitogenic proliferation, phosphorylation of intrace llular proteins, MAP kinase activation, activation of Stats 1, 3, and 5, and induction of target gene expression. Specific cytoplasmic domai ns of the growth hormone receptor mediate Jak2 activation, metabolic a ctions of growth hormone, Stat activation, and calcium influx. (C) 199 8 Churchill Livingstone.